POS0259 A RANDOMIZED CLINICAL TRIAL OF 2-WEEK METHOTREXATE DISCONTINUATION IN RHEUMATOID ARTHRITIS PATIENTS VACCINATED WITH INACTIVATED SARS-COV-2 VACCINE
Authors: C. Scognamiglio Renner Araujo, A. C. Medeiros Ribeiro, C. Saad, K. Bonfiglioli, D. S. Domiciano, A. Yukie Shimabuco, M. Rodrigues Silva, E. Neves, S. Pasoto, T. Pedrosa, L. Kanda Kupa, G. Zou, R. M. Pereira, C. A. Silva, N. Aikawa, E. Bonfa
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with rheumatoid arthritis (RA) on methotrexate have reduced vaccine responses. Temporary discontinuation has improved immunogenicity of anti-influenza vaccine, but this strategy has not been evaluated in anti-SARS-CoV-2 vaccines. Objectives To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in rheumatoid arthritis (RA) patients. Methods This was a single-center, prospective, randomized, investigator-blinded, intervention study (# NCT04754698 , CoronavRheum), including adult RA patients (stable CDAI≤10, prednisone ≤7.5mg/day), randomized (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at D0, D28 and D69. Co-primary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion(SC) and neutralizing antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titers (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and, for safety reasons, those who flared at D28 (CDAI&gt;10) and did not withdraw MTX twice. Results Randomization included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 (MTX-hold) and 69 (MTX-maintain) patients. Further exclusions: 27 patients [13 (21.7%) vs. 14 (20.3%), p=0.848] with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI&gt;10 at D28. At D69, MTX-hold (n=37) had a higher rate of seroconversion than MTX-maintain (n=55) group [29 (78.4%) vs 30 (54.5%), p=0.019], with parallel augmentation in GMT [34.2 (25.2-46.4) vs 16.8 (11.9-23.6), p=0.006]. No differences were observed for NAb positivity [23 (62.2%) vs 27 (49.1%), p=0.217]. At D28 flare, rates were comparable in both groups (CDAI, p=0.122; DAS28-CRP, p=0.576), whereas CDAI&gt;10 was more frequent in MTX-hold at D69 (p=0.024). Figure 1. Conclusion We provide novel data that 2-week MTX withdrawal after each Sinovac-CoronaVac vaccine dose improves anti-SARS-CoV-2 IgG response. The increased flare rates after second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares. References [1]​​Jara A, Undurraga EA, González C, et al. Effectiveness of an inactivated SARS-CoV-2 vaccine in Chile. N Eng J Med . 2021 Sep 2;385(10):875-84. doi: 10.1056/NEJMoa2107715 [2]Furer V, Eviatar T, Zisman D , et al. Lb0003 Immunogenicity and Safety of the BNT162B2 mRNA Covid-19 Vaccine in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases and General Population: a Multicenter Study. Ann Rheum Dis . 2021;80:200-201. doi: 10.1136/annrheumdis-2021-220647 [3]Medeiros-Ribeiro AC, Aikawa NE, Saad CG, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial . Nat. Med . 2021 Jul 30:1-8. doi: 10.1038/s41591-021-01469-5. [4]Park JK, Lee MA, Lee EY, et al. Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2017 Sep 1;76(9):1559-65. http://dx.doi.org/10.1136/annrheumdis-2017-211128 [5]Park JK, Lee YJ, Shin K, et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2018 Jun 1;77(6):898-904. http://dx.doi.org/10.1136/annrheumdis-2018-213222 Acknowledgements This protocol is part of a larger study of immunosuppressed patients with ARD (Clinicaltrials.gov# NCT04754698 ) Disclosure of Interests None declared